Response of epithelial cell cultures to factors which may increase their life span or, conversely, induce terminal differentiation will be studied. The effect of varying media and serum concentrations and method for subculture will be assessed in human epithelial cultures from semen, skin, fetal kidney, and amniotic fluid. We will attempt to prolong the in vitro lifetime of such cultures with epidermal growth factor and tumor promoting agents such as phorbol esters and retinoic acid. Artificial basement membranes constructed on petri dish surfaces from isolated glomerular basement membrane glycoproteins will be tested as substrates for epithelial cultures. Relationship of ABH blood group expression to proliferative potential of epithelial cells will be explored by separating blood group positive and negative epithelial cells by affinity techniques and assessing their subsequent growth. Carcinoma cell lines will be screened to find lines which express ABH antigens. The relationship of ABH expression to terminal differentiation will be studied in separated ABH-positive and negative cells in these lines. We will apply protease inhibitors and other agents to try to induce ABH expression and terminal differentiation in short term epithelial cultures and tumor lines.